Pongo abelii      Atypical/PIKK


※ PIKK family introduction

    Phosphatidylinositol-3 kinase-related kinases (PIKKs) belong to atypical protein kinase group, which share little similarity of kinase catalytic domain. PIKKs family contains six members which are involved in responding to various stresses, including DNA damage, blocks in DNA replication, availability of nutrients and errors in mRNA splicing. The protein kinase domain of PIKKS, located in C-terminus, is always flanked by two conserved domain, known as FAT and FATC domain, which may interact and participate in kinase regulation (1). ATM, one of family member, is involved in responding to a specific type of DNA damage, such as DNA double strand breaks, and controls the cell-cycle progression by phosphorylates multiple substrates including p53 and Chk2. In addition, ATM also locates in cytoplasmic especially in neuronal or neuron-like cells (2). Ataxia telangiectasia and Rad3-related protein (ATR) acts as a DNA damage sensor. Activated by DNA lesions including base adducts, crosslinks, DSBs, and compounds that directly promote replication stress such as hydroxyurea and aphidicolin and phosphorylates multiple substrates to control the DNA replication and mitosis (3). mTOR is a serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. mTOR is regulated by dynamic changes in cellular localization (3). Transformation/transcription domain-associated protein (TRRAP) is also structurally related to the PIKK family. TRRAP proteins (Tra1 in budding yeast) are common components of many histone acetyltransferase (HAT) complexes, and mediate a variety of cellular processes by recruiting HAT complexes to chromatin (4).

Reference
1. Lempiainen, H. and Halazonetis, T.D. (2009) Emerging common themes in regulation of PIKKs and PI3Ks. EMBO J, 28, 3067-3073. PMID: 19779456
2. Yang, D.Q., Halaby, M.J., Li, Y., Hibma, J.C. and Burn, P. (2011) Cytoplasmic ATM protein kinase: an emerging therapeutic target for diabetes, cancer and neuronal degeneration. Drug Discov Today, 16, 332-338. PMID: 21315178
3. Lovejoy, C.A. and Cortez, D. (2009) Common mechanisms of PIKK regulation. DNA Repair (Amst), 8, 1004-1008. PMID: 19464237
4. Kanoh, J. and Yanagida, M. (2007) Tel2: a common partner of PIK-related kinases and a link between DNA checkpoint and nutritional response? Genes Cells, 12, 1301-1304. PMID: 18076567


There are 13 genes.  Reviewed (0 or Unreviewed (13

No.StatusiEKPD IDEnsemble Gene IDUniProt AccessionGene Name
1
iEKPD-Poa-0077
ENSPPYG00000003845.2
H2NF74
ATM
2
iEKPD-Poa-0312
ENSPPYG00000014173.2
H2PBM9
ATR
3
iEKPD-Poa-g005
ENSPPYG00000012025.2
H2P503
PI4KA
4
iEKPD-Poa-0024
ENSPPYG00000000868.1
H2N5W0
PI4KB
5
iEKPD-Poa-0072
ENSPPYG00000003455.2
H2NE05
PIK3C2A
6
iEKPD-Poa-g010
ENSPPYG00000000316.2
H2N417
PIK3C2B
7
iEKPD-Poa-0200
ENSPPYG00000009120.2
H2NW86
PIK3C3
8
iEKPD-Poa-0310
ENSPPYG00000014147.2
H2PBK3
PIK3CB
9
iEKPD-Poa-0045
ENSPPYG00000001909.2
H2N969
PIK3CD
10
iEKPD-Poa-0395
ENSPPYG00000017896.2
H2PN59
PIK3CG
11
iEKPD-Poa-0410
ENSPPYG00000018573.1
H2PQ95
PRKDC
12
iEKPD-Poa-0153
ENSPPYG00000007141.1
H2NQ91
SMG1
13
iEKPD-Poa-0382
ENSPPYG00000017366.2
H2PLH5
TRRAP